Investigating Air Pollution Effects on the Developing Brain and ASD ABSTRACT The goal of this study is to examine the effect of prenatal and early life air pollution exposure on the developing brain, cognitive and adaptive function, and autism spectrum disorder (ASD). Dramatic changes in brain structure and function are well known in early life. The unfolding of autistic behaviors across the first few years of childhood is accompanied by age-specific brain changes that differ between children with ASD and those with typical developmental trajectories. Epidemiologic studies, including our own, suggest that air pollution exposure may increase the risk of ASD and other neurodevelopmental disorders. However, the effect of prenatal and early life air pollution exposure on brain structure and white matter integrity during early childhood has not been studied, though increasing numbers of epidemiologic studies support the presence of neurodevelopmental effects. Here we propose to examine the relationship between prenatal and early life air pollution exposure and longitudinal measures of brain structure and white matter integrity, cognitive and adaptive function, and ASD and related traits in the NIH-funded, Autism Centers of Excellence (ACE) Network Infant Brain Imaging Study (IBIS). IBIS is a unique network of four clinical sites that enroll infants at high or low familial risk for ASD, allowing for contrast of familial genetic influences. Standardized neuroimaging protocols, along with cognitive, behavior, and ASD assessments, were and are being conducted over regular intervals, creating a rich resource for the study of environmental exposures on the developing brain. We will leverage this valuable resource for the first prospective study of prenatal and early life air pollution effects on very early brain development. Specific aims are: (1) to examine the effect of prenatal and early life air pollution exposure on early longitudinal brain development; (2) to evaluate the effect of prenatal and early life air pollution exposure on the early trajectory of cognitive development and adaptive function; and (3) to assess the effect of prenatal and early life air pollution exposure on the development of ASD and dimensional characteristics of autism. Because air pollutant exposure is common and can be mitigated, the potential public health impact of this study is large. Additionally, identification of a risk factor in very young children provides the opportunity for early intervention where reduction of risk for disordered development is still possible.